Lu Zang

The metastasis suppressor, N-myc downregulated gene 1 (NDRG1), is a prognostic biomarker for human colorectal cancer.

Metastasis remains to be one of the most prevalent causes leading to poor long-term survival of colorectal cancer (CRC) patients. The clinical significances of tumor metastatic suppressor, N-myc downregulated gene 1 (NDRG1), have been inconsistently reported in a variety of cancerous diseases. In this study with 240 CRC clinical specimens, we showed that NDRG1 expression was significantly decreased in most of CRC tissues compared to the paired non-tumor counterparts. Statistical analysis revealed a significant inverse correlation of NDRG1 expression with tumor stage, differentiation status and metastasis. Compared with NDRG1-negative group, NDRG1-positve group had better disease-free/overall survival (p = 0.000) over 5 years’ follow-up. Furthermore, NDRG1 was considered to be an independent prognostic factor for overall survival (p = 0.001) and recurrence (p = 0.003). Our study concludes that NDRG1 is a novel favorable predictor for the prognosis in CRC patients.

MicroRNA-301a promotes migration and invasion by targeting TGFBR2 in human colorectal cancer

BackgroundMicroRNAs (miRNAs) have been reported to play crucial roles in regulating a variety of genes pivotal for tumor metastasis. MicroRNA-301a (miR-301a) is overexpressed and displays oncogenic activity in many cancers. However, little is known about the potential roles of miR-301a in colorectal cancer (CRC).MethodsTaqman probe stem-loop real-time PCR was used to quantitatively measure the expression level of miR-301a in 48 cases of CRC tissues and the matched adjacent non-tumor mucosa as well as in CRC cell lines. miR-301a mimics and inhibitors were used to up-regulate and down-regulate miR-301a in CRC cells, respectively; lentivirus was used to construct miR-301a stably up- and down-regulated CRC cell lines. Metastasis ability was evaluated by transwell and wound healing assays while invasion was measured by transwell coated with matrix gel in vitro; in vivo metastasis was performed on nude mice model. The target of miR-301a was predicted by TargetScan software and validated by qRT-PCR, immunohistochemistry, western blot and luciferase reporter gene assay.ResultsThe expression of miR-301a was significantly higher in lymph node metastasis positive CRC samples compared with negative ones. Downregulation of miR-301a significantly inhibited the migration and invasion both in vitro and in vivo while forced up-regulation of miR-301a promoted migration and invasion. TGFBR2 was identified to be the downstream target of miR-301a. Knockdown of TGFBR2 in cells treated by miR-301a inhibitor elevated the previously abrogated migration and invasion.ConclusionsOur data indicated that miR-301a correlated with the metastatic and invasive ability in human colorectal cancers and miR-301a exerted its role as oncogene by targeting TGFBR2.

Long-term outcome of laparoscopic total mesorectal excision for middle and low rectal cancer

Abstract This study aimed to assess the feasibility and long-term outcome of laparoscopic total mesorectal excision for middle and lower rectal cancer. Retrospective assessment was performed on 612 patients with middle and low rectal cancer in the surgery department of our hospital. Three-hundred and three patients underwent laparoscopic total mesorectal excision (LTME), and 309 patients underwent open TME (OTME). All the data regarding patient details, operative variables and the short- and long-term outcomes were collected and compared. The sphincter-preserving rates of the two groups were similar. The conversion rate in LTME was 2.31% (seven cases). Fourteen cases (6.67%) of protective diverting stoma were fashioned in the LTME group compared with 57 cases (26.64%) in the OTME group. The postoperative morbidity was the same in these two groups, while the postoperative period until bowel movement and hospital discharge was shorter in the LTME group (P < 0.01). The median follow-up period was 34 (6–81) months for the LTME group and 36 (6–81) months for the OTME group. Local recurrence rates, the five-year disease-free survival rate and the five-year overall survival rate showed no difference between the two groups. Laparoscopic surgery is feasible and safe in patients with middle and lower rectal caner and can provide favorable short-term and long-term outcomes.

Downregulation of GRHL2 inhibits the proliferation of colorectal cancer cells by targeting ZEB1

Previous reports have associated GRHL2 with tumor progression. However, the biological role of GRHL2 in human colorectal cancer (CRC) has not been explored. We examined the expression of GRHL2 in 75 CRC samples, as well as the paired non-tumor tissues, by immunohistochemistry, qRT-PCR, and western blot analysis. The association between GRHL2 expression and various clinicopathological parameters including Ki-67, a marker of proliferative activity, was also evaluated. We performed lentivirus-mediated shRNA transfection to knock down GRHL2 gene expression in HT29 and HCT116 CRC cells. Cell proliferation was examined by the CCK-8 (Cell Counting Kit-8) assay, colony formation, and cell cycle assay in vitro. Tumorigenesis in vivo was assessed using a mouse xenograft model. Moreover, we transiently silenced ZEB1 expression in GRHL2-knockdown CRC cells using specific shRNA, and then examined the effects on GRHL2 and E-cadherin expression, as well as cell proliferation. Herein, we demonstrated that enhanced GRHL2 expression was detected in CRC, and correlated with higher levels of Ki-67 staining, larger tumor size, and advanced clinical stage. Knocking down GRHL2 in HT29 and HCT116 CRC cells significantly inhibited cell proliferation by decreasing the number of cells in S phase and increasing that in the G0/G1 phaseof the cell cycle. This resulted in inhibition of tumorigenesis in vivo, as well as increased expression of ZEB1. Furthermore, transient ZEB1 knockdown dramatically enhanced cell proliferation and increased GRHL2 and E-cadherin expression. Collectively, our study has identified ZEB1 as a target of GRHL2 and suggested a reciprocal GRHL2-ZEB1 repressive relationship, providing a novel mechanism through which proliferation may be modulated in CRC cells.

The NAD(P)H: quinine oxidoreductase 1 (NQO1) gene 609 C>T polymorphism is associated with gastric cancer risk: evidence from a case-control study and a meta-analysis.

UNLABELLED The association between the NAD(P)H quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and gastric cancer has been widely evaluated, but a definitive answer is so far lacking. We first conducted a case-control study to assess this association in a large Han Chinese population, and then performed a meta-analysis to further address this issue. Although our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between gastric cancer patients and controls, in the meta analysis involving 4,000 subjects, comparison of alleles 609T and 609C indicated a significantly increased risk (46%) for gastric cancer (95% confidence interval (95%CI) for odds ratio (OR)=1.20- 1.79) in individuals with the T allele. The tendency was similar to the homozygote (OR=1.81, 95%CI: 1.16-2.84), dominant models (OR=1.41, 95%CI: 1.12-1.79), as well as recessive model (OR=1.58, 95%CI: 1.06-2.35). Stratified analysis by study design demonstrated stronger associations in population-based than in hospital-based studies. And ethnicity-based analysis demonstrated a significant association in Asians. We conclude that the NQO1 gene C609T polymorphism increases the risk for gastric cancer, especially in Asian populations.

Cancer-Associated-Fibroblast Induces Epithelial-Mesenchymal Transitionof Gastric Cancer Cells via Activating Thy-1

Cancer-associated fibroblasts (CAFs) are the key stromal cells in solid tumor microenvironment and are crucial for facilitating tumor metastasis. However, the detailed mechanism of how CAFs induce metastasis in human gastric cancer remains to be elucidated. In this study, using the CAFs isolated from human gastric tumor tissues, we have demonstrated that co-culturing of the CAFs with gastric cancer cells could activate the epithelial-mesenchymal transition (EMT) program, leading to enhanced cancer cell migration and invasion. In the CAF cells, Thy-1 expression was significantly increased, compared to the normal fibroblasts. Mechanistic studies revealed that depletion of Thy- 1 by siRNA in CAF cells attenuated the CAFs-induced EMT and aggressiveness in gastric cancer cells. Taken together, our studies indicate a significant role of Thy-1 in CAFs-induced gastric cancer progression. Targeting Thy-1 could be a potential therapeutic strategy for gastric cancer treatment.

Laparoscopic sphincter-preserving surgery for low rectal tumor using prolapsing technique

Introduction: With this study, we aimed to assess the feasibility and outcome of laparoscopy‐assisted low anterior resection with a prolapsing technique for low rectal tumors.

Laparoscopic abdominoperineal resection with trans-abdominal individualized levator transection: interim analysis of a randomized controlled trial

Extralevator abdominoperineal excision (ELAPR) is challenging ‘conventional’ abdominoperineal excision (APR), yet the safety and efficacy of ELAPR is still under debate. We therefore developed a laparoscopic APR with trans‐abdominal individualized levator transection (LAPR‐TILT) approach and compared the outcome with a conventional laparoscopic APR (CLAPR).

Multiple Polypoid Colonic Metastases from Primary Gastric Signet Ring Cell Carcinoma

To the Editor: Gastric carcinoma is a common gastrointestinal (GI) malignancy while signet ring cell carcinoma (SRCC) is a well-known poorly differentiated histological type that has a strong tendency for metastasis. The dissemination of gastric carcinoma mainly presents in three patterns. The most common approach for metastasis is through the regional lymph node. Hematogenous spread is also very common and mostly occurs in the liver, lungs, bones, and adrenal gland. In addition, direct adjacent invasion, peritoneal seeding, and Krukenberg tumor are less seen but are also very important in clinic with poor prognosis. In this report, we present a case of rare colonic metastases in the form of multiple polyps from primary gastric SRCC.

Prevention and management of hemorrhage during a laparoscopic colorectal surgery

Laparoscopy is believed to play an important role in the treatment for colorectal cancer and is now extensively applied across the world. Although the safety and feasibility of laparoscopic colorectal surgery has been verified by several randomized controlled trials, intraoperative hemorrhage is still a challenge for clinicians, which could lead to conversion to laparotomy or increased mortality. In this article we discuss the strategy for prevention and management of hemorrhage in laparoscopic colorectal surgery in terms of anatomy and surgical skills.